Journal Article

Antibodies to the Glycoprotein GP2 Subunit Cross-React between Old and New World Arenaviruses

Hastie, Kathryn M., Duehr, James, Krammer, Florian, Oestereich, Lisa, Amanat, Fatima, Saphire, Erica Ollmann

2018

Overview

Several viruses in the Arenaviridae family infect humans and cause severe hemorrhagic fevers which lead to high case fatality rates. Due to their pathogenicity and geographic tropisms, these viruses remain very understudied. As a result, an effective vaccine or therapy is urgently needed. Here, we describe efforts to produce cross-reactive monoclonal antibodies that bind to both New and Old World arenaviruses. All of our MAbs seem to be nonneutralizing and nonprotective and target subunit 2 of the glycoprotein. Due to the lack of reagents such as recombinant glycoproteins and antibodies for rapid detection assays, our MAbs could be beneficial as analytic and diagnostic tools. Arenaviruses pose a major public health threat and cause numerous infections in humans each year. Although most viruses belonging to this family do not cause disease in humans, some arenaviruses, such as Lassa virus and Machupo virus, are the etiological agents of lethal hemorrhagic fevers. The absence of a currently licensed vaccine and the highly pathogenic nature of these viruses both make the necessity of developing viable vaccines and therapeutics all the more urgent. Arenaviruses have a single glycoprotein on the surface of virions, the glycoprotein complex (GPC), and this protein can be used as a target for vaccine development. Here, we describe immunization strategies to generate monoclonal antibodies (MAbs) that cross-react between the glycoprotein complexes of both Old World and New World arenaviruses. Several monoclonal antibodies isolated from immunized mice were highly cross-reactive, binding a range of Old World arenavirus glycoproteins, including that of Lassa virus. One such monoclonal antibody, KL-AV-2A1, bound to GPCs of both New World and Old World viruses, including Lassa and Machupo viruses. These cross-reactive antibodies bound to epitopes present on the glycoprotein 2 subunit of the glycoprotein complex, which is relatively conserved among arenaviruses. Monoclonal antibodies binding to these epitopes, however, did not inhibit viral entry as they failed to neutralize a replication-competent vesicular stomatitis virus pseudotyped with the Lassa virus glycoprotein complex in vitro . In addition, no protection from virus challenge was observed in in vivo mouse models. Even so, these monoclonal antibodies might still prove to be useful in the development of clinical and diagnostic assays. IMPORTANCE Several viruses in the Arenaviridae family infect humans and cause severe hemorrhagic fevers which lead to high case fatality rates. Due to their pathogenicity and geographic tropisms, these viruses remain very understudied. As a result, an effective vaccine or therapy is urgently needed. Here, we describe efforts to produce cross-reactive monoclonal antibodies that bind to both New and Old World arenaviruses. All of our MAbs seem to be nonneutralizing and nonprotective and target subunit 2 of the glycoprotein. Due to the lack of reagents such as recombinant glycoproteins and antibodies for rapid detection assays, our MAbs could be beneficial as analytic and diagnostic tools.

• Publisher: American Society for Microbiology
• Subject: Amino acids / Animal models / Animals / Antibodies, Monoclonal - immunology / Antibodies, Viral - immunology / Antibodies, Viral - isolation & purification / Arenaviridae Infections - immunology / Arenaviridae Infections - prevention & control / arenaviruses / Arenaviruses, New World - immunology / Arenaviruses, Old World - immunology / Cloning / Cross Reactions / Disease Models, Animal / Epitope Mapping / Epitopes / Epitopes, B-Lymphocyte - immunology / Genomes / Glycoproteins / Glycoproteins - immunology / GP2 / GPC / Hemorrhage / Immunization / Immunoglobulins / Junin / Lassa / Machupo / Mice / Monoclonal antibodies / Mus musculus / Pathogenicity / Phylogenetics / Proteins / Public health / Stomatitis / Vaccine development / Vaccines / Viral Structural Proteins - immunology / Virions / Viruses